TY - JOUR
T1 - Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology
AU - Groseth, Allison
AU - Gardner, Don
AU - Meade-White, Kimberly
AU - Amler, Susanne
AU - Ebihara, Hideki
N1 - Publisher Copyright:
© 2023, Public Library of Science. All rights reserved.
PY - 2023/5
Y1 - 2023/5
N2 - Background Bunyavirus infections, including those caused by Bunyamwera serogroup orthobunya-viruses, represent a significant and yet likely still vastly underappreciated cause of mild to moderate human febrile infections. In severe cases, these infections can also cause neurological disease, particularly meningitis and encephalitis, and infection can even be fatal. However, with a few exceptions, information regarding the mechanisms underlying the neu-roinvasion and neuropathogenesis of such infections is limited. This is due in part to a lack of animal models to facilitate such studies. Methodology/Principal findings In an effort to develop an immunocompetent model of infection with Bunyamwera serogroup orthobunyaviruses, we infected 4-6-week-old female hamsters via either the intraperitoneal or subcutaneous route with 106 pfu/animal of Bunyamwera virus (BUNV), Batai virus or Ngari virus. Only BUNV infection resulted in clinical disease, which was characterized by weight loss, lethargy and neurological signs (i.e. tremor of the head or limbs, loss of righting reflex, “waltzing”). While symptoms were of similar severity for both routes, they occurred more frequently following subcutaneous inoculation. Consistent with these clinical signs, both antigen staining and histopathological abnormalities were found extensively throughout the brain. Conclusions/Significance The reported hamster model of BUNV infection provides a new tool for studying orthobunya-virus infection, and particularly neuroinvasion and the development of neuropathology. This model is particularly significant because it makes use of immunologically competent animals and relies on a subcutaneous inoculation route that more closely mimics the natural infection route for arboviruses, thereby providing a more authentic cellular and immunological context at the initial site of infection.
AB - Background Bunyavirus infections, including those caused by Bunyamwera serogroup orthobunya-viruses, represent a significant and yet likely still vastly underappreciated cause of mild to moderate human febrile infections. In severe cases, these infections can also cause neurological disease, particularly meningitis and encephalitis, and infection can even be fatal. However, with a few exceptions, information regarding the mechanisms underlying the neu-roinvasion and neuropathogenesis of such infections is limited. This is due in part to a lack of animal models to facilitate such studies. Methodology/Principal findings In an effort to develop an immunocompetent model of infection with Bunyamwera serogroup orthobunyaviruses, we infected 4-6-week-old female hamsters via either the intraperitoneal or subcutaneous route with 106 pfu/animal of Bunyamwera virus (BUNV), Batai virus or Ngari virus. Only BUNV infection resulted in clinical disease, which was characterized by weight loss, lethargy and neurological signs (i.e. tremor of the head or limbs, loss of righting reflex, “waltzing”). While symptoms were of similar severity for both routes, they occurred more frequently following subcutaneous inoculation. Consistent with these clinical signs, both antigen staining and histopathological abnormalities were found extensively throughout the brain. Conclusions/Significance The reported hamster model of BUNV infection provides a new tool for studying orthobunya-virus infection, and particularly neuroinvasion and the development of neuropathology. This model is particularly significant because it makes use of immunologically competent animals and relies on a subcutaneous inoculation route that more closely mimics the natural infection route for arboviruses, thereby providing a more authentic cellular and immunological context at the initial site of infection.
UR - http://www.scopus.com/inward/record.url?scp=85160373362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85160373362&partnerID=8YFLogxK
U2 - 10.1371/journal.pntd.0011355
DO - 10.1371/journal.pntd.0011355
M3 - Article
C2 - 37235549
AN - SCOPUS:85160373362
SN - 1935-2727
VL - 17
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 5
M1 - e0011355
ER -